\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art novel imaging techniques by focusing on the most important evidence-based developments in this area.
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"d9159ce31733bf78cc2a79b18c225994",bookSignature:"Dr. Gabriel Cismaru",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11867.jpg",keywords:"Hypertrophic Cardiomyopathy, Dilated Cardiomyopathy, Restrictive Cardiomyopathy, Transesophageal Echocardiography, Intracardiac Echocardiography, 3-Dimensional Echocardiography, Adult Congenital Heart Disease, Tetralogy of Fallot, Transposition of the Great Vessels, Coronary Artery Disease, Risk Stratification, Revascularization",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 21st 2022",dateEndSecondStepPublish:"May 19th 2022",dateEndThirdStepPublish:"July 18th 2022",dateEndFourthStepPublish:"October 6th 2022",dateEndFifthStepPublish:"December 5th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Cismaru Gabriel is an Assistant Professor at the University of Medicine and Pharmacy Cluj-Napoca, certified in Cardiology. After completing his certification in cardiology, Dr. Cismaru began his electrophysiology fellowship at the Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu. He has authored or co-authored peer-reviewed articles and book chapters in the field of cardiac pacing, defibrillation, electrophysiological study, and catheter ablation.",coeditorOneBiosketch:"Raluca Tomoaia is an MD, Ph.D. in novel techniques in Echocardiography at the University of Medicine and Pharmacy in Cluj-Napoca, Romania., assistant professor, and a researcher in echocardiography and cardiovascular imaging.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"191888",title:"Dr.",name:"Gabriel",middleName:null,surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru",profilePictureURL:"https://mts.intechopen.com/storage/users/191888/images/system/191888.png",biography:"Dr. Cismaru Gabriel is an assistant professor at the Cluj-Napoca University of Medicine and Pharmacy, Romania, where he has been qualified in cardiology since 2011. He obtained his Ph.D. in medicine with a research thesis on electrophysiology and pro-arrhythmic drugs in 2016. Dr. Cismaru began his electrophysiology fellowship at the Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, France, after finishing his cardiology certification with stages in Clermont-Ferrand and Dinan, France. He began working at the Rehabilitation Hospital\\'s Electrophysiology Laboratory in Cluj-Napoca in 2011. He is an experienced operator who can implant pacemakers, CRTs, and ICDs, as well as perform catheter ablation of supraventricular and ventricular arrhythmias such as ventricular tachycardia and ventricular fibrillation. He has been qualified in pediatric cardiology since 2022, and he regularly performs device implantation and catheter ablation in children. 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Reviewing the methodology and case study, this chapter explores the effectiveness, characteristics, and future prospects of the methodology. The discussion section also examines the capability of the methodology for the two significant changes, namely climate change and aging population, which have been presented in Chapter 1. Furthermore, the same section discusses how this methodology deals with the remaining issues in the existing Japanese systems, which have been raised in Chapter 2. After that, the final section summarizes the conclusions of the studies.
This section discusses the results of this study from the following five perspectives: (1) effects of the methodology for promoting sustainable home design, (2) characteristics of the methodology, (3) coordination with the existing systems, (4) applicability of the methodology, and (5) future research.
As illustrated in the case study, we have designed a detached house, following the methodology for promoting sustainable home design. That is to say, we have designed the house’s parts or elements, so that the elements’ variables satisfy their desired values as much as possible. After the house began to be used, we have obtained objective evaluations of the home’s environmental and sustainability performance as well as various comments on the home from the occupants and visitors.
First, all of the objective and quantitative evaluations have shown that the home has considerably high environmental performance. According to CASBEE for detached houses, a comprehensive assessment system, the home has readily been ranked in the highest “S,” with an extremely high score of built environment efficiency (BEE). Subsequently, the house has been classified into the highest “five star” by life cycle carbon minus (LCCM) certification, due to its higher energy saving performance and larger solar energy generation capacity. Meanwhile, the energy usage comparison with the average home has shown that the total energy usage of this home is equal to about 27% of the average home under the same conditions. The water usage comparison with the average home has also proved the higher water saving performance of this home. In addition, such high environmental performance has been highly evaluated when this house received the prize at the Sustainable Housing Awards.
The reactions of the occupants and visitors suggest that following the methodology has produced various favorable effects. On the other hand, any unfavorable side effects of utilizing the methodology have not been observed thus far. “Higher thermal insulation performance” has contributed to improve the occupant’s allergy symptoms, as well as improving comfort and reducing demand for heating and air-conditioning. “Placing areas relating to water use and hot water supply” has brought about reduction in time until hot water comes out, in addition to the reduction in materials for piping and energy for hot water supply. “Taking accessible and universal design into spatial elements, such as doorways and main access route to the entrance,” has already brought about present safety and comfort, above and beyond preparing the occupants for the future. “Protection of glass against impacts with shutters” has also contributed to prevent crimes and increase thermal performance, in addition to reduce the risk of being damaged by impacts such as fire and serious extreme weather events.
In this way, we have evaluated the home, which has been designed closely based on the methodology, from both the quantitative analyses and reactions of occupants and visitors. First, all of the quantitative analyses have shown that the home has significantly high environmental performance. The reactions of the occupants and visitors have also suggested that this home is comprehensively sustainable and comfortable. These assessment results indicate that if system users closely follow the methodology, they can comprehensively realize sustainable homes, which have high environmental performance.
The characteristics of the methodology includes (1) visualization of the whole picture for promoting sustainable home design, (2) user-friendliness, (3) comprehensiveness, (4) adaptability to regional differences, and (5) flexibility toward changes over time.
In addition,
Figure 5 in Chapter 4 has demonstrated the control system for promoting sustainable home design. This figure basically contains “sustainability,” “environmental, social, and economic problems,” and “disturbances” as system components. Moreover, “adaptation” to disturbances has been incorporated as a route to sustainability, as well as “solution” or “prevention” of the problems. Utilizing this basic scheme, this figure inclusively shows processes for promoting sustainable design on both new and existing homes with the “sustainable design guidelines” and “sustainability checklist.”
We consider that Figure 5 in Chapter 4 concisely explains the whole picture of the sustainable design processes with the guidelines and checklist. Accordingly, we expect that this visualization itself helps people concerned to easily understand that whole picture.
The “material and spatial elements” in the sustainable design guidelines and sustainability checklist are equal to “actual parts of houses.” Thus, the system users can smoothly design, check, evaluate, and inspect the house, by easily comparing the drawings or actual house with the guidelines or checklist [2]. In fact, the design process in the case study has supported the user-friendliness of the guidelines and checklist; the designers of the homebuilder readily accepted them and efficiently made the house’s drawings [2]. In addition, “correspondence between the elements and actual parts of houses” is unique to this methodology. On the other hand, the major existing Japanese methods, namely the housing performance indication system (HPIS), long-life quality housing (LQH) certification, and CASBEE for detached houses, do not possess this characteristic, as shown in Chapter 2.
Meanwhile, user-friendliness basically requires such methods to be “not complex” and “not long.” As cited before,
Originally, the “sustainable design guidelines” has been aimed comprehensively at showing the relationships between the standard home and sustainability. Therefore, we expected that following this methodology would lead to achieve comprehensive sustainable homes. The evaluation results of the home in the case study have been obtained as we expected. The CASBEE assessment results, namely the very high BEE score and high scores in all the six categories (Figure 14 in Chapter 5), have supported the comprehensiveness of the methodology as well as the comprehensive sustainability of that home.
This methodology, more specific the “element - variable - desired value” structure in the “sustainable design guidelines” and “sustainability checklist,” originally has a mechanism of easily adapting to regional differences. As shown in Figure 3 in Chapter 3, examining the relationships between important elements and stability conditions, system designers determine the elements’ variables and their desired values. This determination process has a mechanism of reflecting a variety of regional characteristics, including natural, geographical, social, and cultural features [2].
For instance, “resistance to earthquakes,” a variable of the framework, reflects a geological feature of Japan, namely “earthquake-prone.” This mechanism also enables the system designers to readily vary the guidelines, according to the region’s characteristics [2]. For example, if the region is in a strong wind area or snowy area, they can easily adjust the guidelines to the region, by adding “resistance to wind” or “resistance to snow load” as a variable of the framework [2].
Another example of reflecting regional features is “heat insulation” of the bathtub. We have attached importance to this variable, due to a Japanese cultural feature. Reducing heat loss from bath is important in Japan since people frequently take a bath and usually share the same hot water in the bathtub with their family members. On the other hand, in societies without such a lifestyle, it is easy for system designers to simply omit this variable.
The “element – variable – desired value” structure in the guidelines and checklist also leads to flexibility toward changes over time. Figure 1 explains this characteristic, mainly focusing on two major global changes progressing in the twenty-first century, namely “climate change” and “aging population.”
Flexibility of the methodology toward changes over time.
First, the course from “climate change” toward the materials or spatial elements passes through “mitigation measures/adaptation measures.” This course shows that system designers can take necessary mitigation/adaptation measures against climate change, by adjusting relevant elements, variables, and desired values. For example, when taking a measure of “improving thermal insulation performance,” we have added a variable “thermal insulation performance” to two material elements, namely “thermal insulation” and “windows and doors.” Similarly, we have easily taken an adaptation measure, by adding “protection of glass against impact” and “with shutters” as a variable and its desired value of the material element, “windows and doors.”
In addition, the broken dividing line between “mitigation measures” and “adaptation measures” in the block means that the two types of measures overlap each other. Such overlapping measures include “improving thermal insulation performance,” “harnessing natural energy,” “utilizing rainwater,” and “improving natural ventilation.” For instance, “improving thermal insulation performance” contributes to not only saving energy through reducing demand for heating and air-conditioning but also increasing resilience in extreme weather and crises.
On the other hand, Figure 1 shows two courses from “aging population” toward the material or spatial elements, that is, the routes through “mitigation measures/adaptation measures” and “accessible and universal design.” The broken line that connects “aging population” and “mitigation measures/adaptation measures” means that some of mitigation/adaptation measures benefit elderly people’s health. For example, “improving thermal insulation performance” can reduce the number of elderly people’s deaths and illnesses resulting from indoor coldness in cold weather. Likewise, “improving thermal insulation performance” and “improving natural ventilation” are expected to decrease heat stroke patients and deaths of the elderly in hot weather.
Meanwhile, the course through “accessible and universal design” represents that system designers can adopt accessible and universal design, by adjusting relevant elements, variables, and desired values. To be concrete, when compiling the guidelines, we first identified spatial elements related to such design, including “specified bedroom,” “doorways,” “stairs,” and “slope.” Subsequently, we have added necessary variables to these elements and set their desired values, so as to adopt accessible and universal design.
Furthermore, Figure 1 contains another change over time, that is, “technological changes.” Technological changes, including innovation in technology, are directly related with material elements; therefore, system designers can efficiently take such changes to relevant material elements. For instance, in the latest revision, we have easily taken “LED” as the desired value of “type of light” of “lighting fixtures.”
From the beginning, we have intended that this methodology is not used independently but coordinated with the existing Japanese systems that have been shown in Chapter 2. Such coordination is expected to exert favorable influences on the utilization of not only this methodology but also the existing methods.
First, when compiling the “guidelines” and “checklist,” we have aimed to provide reliability and incentives to utilize them. The guidelines and checklist use standard grades in the Japan housing performance indication standards (JHPIS) and assessment levels in CASBEE for detached houses, as the desired values of many variables. The JHPIS and CASBEE for detached houses, both of which are national systems, include technical information related to sustainable housing in the descriptions of the standard grades or assessment levels. Accordingly, when referring to the relevant descriptions in the JHPIS and CASBEE for detached houses, system users can obtain reliable related information or technical knowledge about the matters. Meanwhile, following the guidelines enables system users to receive a long-life quality housing (LQH) certification and higher ratings in CASBEE for detached houses. Obtaining a LQH certification leads to preferential treatment from the government, including tax credits; therefore, it can be an incentive for people to use the functions. Moreover, LQH-certified houses and CASBEE higher rated houses have a possibility of competitive superiority in the real estate market. Certified green or sustainable buildings have not yet gained obvious advantages in asset values in the Japanese real estate market, as shown in Chapter 2. However, such competitive superiority is expected to be established sooner or later also in Japan; therefore, it must be another incentive to use the functions.
On the other hand, the utilization of the user-friendly guidelines and checklist has a possibility of promoting the use of the existing public methods. Since the guidelines and checklist refer to CASBEE for detached houses, using these functions naturally leads to the utilization of this trustworthy system but relatively unknown system. Furthermore, when using the “checklist” for inspection or evaluation of existing homes, as a matter of course, “people involved” refer to the “JHPIS (for existing homes)” and “CASBEE for detached houses (existing building),” both of which have hardly been used thus far. The above coordination is expected to produce a synergy effect toward promoting sustainable housing design.
As demonstrated in Section 2.2.4., this methodology, more specific the “sustainable design guidelines” and “sustainability checklist,” has a feature of being adaptable to regional differences. Accordingly, it will be not difficult for system designers in another region to adapt these practical functions for that region [2]. That is to say, the system designers can make its regional version, through the examination of the elements and the adaptation of the elements’ variables and their desired values to the region’s characteristics [2].
As a matter of course, this methodology can be applied to other countries, as well as other regions. When system designers make the guidelines and checklist in other countries besides Japan, they specify variables and their desired values, referring to systems related to buildings and housing used in that country. In such cases, there are two main approaches: (1) specification based on the standards required by building codes and (2) use of criteria shown in voluntary systems related to sustainable housing.
(1) Specification based on the standards required by building codes
If the variables are within the scope of the country’s building codes, it is necessary for the system designers to search the building codes for the variables’ desired values. Building codes specify the “minimum standards” for constructed objects, in order to protect public health, safety, and general welfare [4]. If system designers consider that the standard value required by the building codes is insufficient for the desired value, they make an addition to the standard value, so as to suit the desired value. On the other hand, if they consider that the standard value is suitable to the desired value, they can use it as it is. In the latter case, the variable and its desired value can be omitted from the guidelines and checklist, for people who naturally conform to the building codes, which have legal force.
In fact, Tables 2 and 4 in Chapter 4 also include variables and their desired values, which have been specified based on the above approach. For example, when determining the desired value of “ratio of total window area to floor area in each living space,” a variable of “position and area of windows,” we have made an addition to the standard value required by the Building Standards Act of Japan, namely “1/7 (14.3%) or more,” and set the desired value at “20% or more.” Moreover, “JHPIS 1.1: Grade 2 or over,” the desired value of “resistance to earthquakes” of “framework,” has been originally determined, based on the standard required by the building code. To be concrete, “Grade 2” in this desired value means 1.25 times the strength of an earthquake stipulated in the Building Standards Act of Japan. In addition, “resistance to winds” and “resistance to snow load” are possible variables of “framework” that have been omitted from the tables, because the standards for these two required by the building code have been considered to be suitable to their desired values.
(2) Use of criteria shown in voluntary systems related to sustainable housing
The second approach is to utilize criteria shown in voluntary systems related to sustainable housing, which is especially important outside the scope of building codes. Various kinds of systems or methods for sustainable housing, including assessment and rating systems, standards, and guidelines, are used in many countries of the world [5]. Moreover, energy conservation standards or energy consumption labeling systems for appliances and equipment are also used in many countries [6]. Such voluntary systems or methods usually include criteria, such as grades, levels, classes, target figures, or guideline values. Accordingly, referring to such existing voluntary systems, system designers can select suitable criteria to the desired values of variables. In addition, even if there are not exactly suitable criteria, referring to relevant systems and criteria usually provide system designers with information closely related to the variables and their desired values and help them determine the desired values.
In Tables 2 and 4 of Chapter 4, a high percentage of variables’ desired values have been specified, based on this second approach. In particular, referring to the JHPIS and CASBEE for detached houses, we have selected appropriate grades or levels to the desired values of many variables. We have also used the long-life quality housing (LQH) certification criteria, when setting the desired values of several variables, including “total floor area.” When determining the variable of “appliances” and its desired value, we have utilized the energy-saving labeling system of Japan. Furthermore, consulting several accessible and universal design guidelines has led us to specify the desired values of variables related to universal design, such as “grade of steepness” (slope).
In short, system designers in each country can compile the guidelines and checklist, referring to compulsory and voluntary systems related to buildings and housing used in that country.
Theoretically, the methodology can be applied to various categories of human activities. In other words, in the control system for promoting sustainable home design (Figure 5 in Chapter 4), “homes” in the block of “controlled objects” can be replaced with other categories of human activities [2]. Possibility of such replacement depends on if the table of relationships or the “sustainable design guidelines” can be compiled or not [2].
It will be probably easy to apply it to other types of buildings besides the home, because the structure is similar to one another [2]. It is also possible in theory to apply it to other kinds of infrastructure, including roads and parks [2]. Moreover, we consider it possible to apply the methodology to more large-scale and complex objects, including the city and town, for they are also considered as the complex of material and spatial elements [2].
The case study has supported the effectiveness of the methodology for promoting sustainable housing design. However, we are necessary to conduct further case studies, applying it to both new and existing houses. We expect that the increase of application cases also leads to an increase in the reliability of the methodology and help it to be widely used [2].
The “sustainable design guidelines” and “sustainability checklist” need to be updated, as occasion requires. Such occasion is projected to occur due to several causes, for instance, changes in the natural and social environment, developments in related sciences, innovations in related technologies, and response to the results of case studies [2]. Moreover, through such revision or update processes, we are going to investigate how to revise them efficiently.
This study has demonstrated the methodology for sustainable housing design by applying control science, with a case study. The main point of the methodology is the control system for promoting sustainable housing design with the sustainable design guidelines and sustainability checklist. Utilizing this methodology, we have actually designed a home and built it. The evaluations of the home indicate that closely following the methodology leads to comprehensively achieving sustainable homes with high environmental performance.
Meanwhile, we have pointed out several characteristics of the methodology, in addition to comprehensiveness. First, the diagram of the control system itself is beneficial because it concisely shows the whole picture of the sustainable design processes on both new and existing homes. Second, the “sustainable design guidelines” and “sustainability checklist” are user-friendly since the material and spatial elements are equivalent to real parts of homes. Moreover, the “element – variable – desired value” structure in the guidelines and checklist is superior in “adaptability to regional differences” and “flexibility toward changes over time.”
In the twenty-first century, homes need to be transformed into those which contribute to deal with various issues, including climate change and financial problems due to aging population. Curbing the progress of climate change is a global challenge; therefore, mitigation measures have to be taken into homes all over the world. On the other hand, type and severity of impacts caused by climate change are different, depending on the region. Accordingly, appropriate adaptation measures need to be adopted in homes, in accordance with the predicted impacts in that region. Meanwhile, progressing aging population requires the inclusion of accessible and universal design into homes, in order to increase mobility of occupants and prevent injuries. Homes are used for a very long time; homes which are built or renovated now are expected to be used throughout the twenty-first century. Accordingly, such considerations toward sustainability need to be comprehensively taken into homes from the beginning.
Facing these circumstances, this user-friendly, comprehensive, adaptable, and flexible methodology is effective to promote sustainable housing design in various regions and countries. The guidelines and checklist shown in Tables 2 and 4 in Chapter 4 have been already compatible with climate change and aging population. These tables, which have been compiled to suit features in Japan, can be easily modified to fit features in other regions. Due to the same characteristic of this methodology, these tables can also be readily customized, so as to adapt to predicted impacts in each region caused by climate change. Hence, we expect that this methodology is used in various regions and countries, so as to facilitate sustainable home design.
The case study has successfully demonstrated the effects of the methodology on achieving sustainable homes. However, in order to confirm the effects, we need to conduct more case studies, applying it to both new and existing homes. Moreover, we will have to revise the “guidelines” and “checklist,” as the occasion arises. Through such revision processes, we are planning to examine how to revise them efficiently. Meanwhile, it is theoretically possible to apply this methodology to other categories of human activities, which are regarded as the complex of material and spatial elements. We are also aiming to apply this methodology to more complex and larger scale human activities, such as the city and town.
Multiple sclerosis (MS) is the most prevalent neurological disease among young adults in developed countries, with approximately 2.8 million people being affected worldwide [1]. It principally affects women in their prime, with diagnosis typically occurring between the ages of 20 and 40. The disease is debilitating due to central nervous system (CNS) damage resulting from activated lymphocytes migrating across the blood brain barrier (BBB) and engaging in a proinflammatory response. This causes cells to attack and destroy the myelin sheaths that coat the axons of neurons of the brain, spinal cord and optic nerve, as well as the myelinating cells or oligodendrocytes, and the axons themselves [2]. As neurons receive sensory input from external sources and send motor commands to the muscles by relaying interneuron electrical impulses, breakdown causes interruption to the signals being sent around the body, and dependent on where the damage occurs, results in different signs and symptoms. These can include vision impairment, muscle spasms and numbness, bladder and bowel issues, fatigue and difficulty walking [3]. Most people with MS have progressive neurological disability which, though not usual, can culminate in death [4]. The area of damage or scarring caused by the immune system attack is called a lesion or plaque, and can be visualised by magnetic resonance imaging (MRI). A definitive diagnosis of MS is made when these plaques are shown to be reoccurring and when there is the clear presence of clinical symptoms [3].
Two major types of MS have been recognised, primary progressive multiple sclerosis (PPMS), diagnosed in approximately 15% of patients and which results in steady progression of disease from onset, and relapsing remitting multiple sclerosis (RRMS), which affects approximately 80% of patients and is characterised by periods of relapse separated by periods of remit without worsening of symptoms [5, 6, 7]. Most patients with an initial diagnosis of RRMS will, within 20 years of diagnosis, progress to secondary progressive multiple sclerosis (SPMS) where the stages between relapse and remit shorten and there is a steady decline with an increase in symptoms and disease progression [8]. Up to approximately 5% of MS patients have progressive relapsing multiple sclerosis (PRMS) and this characterised by steady disease progression with occasional relapses [9].
The exact cause of MS is still unknown, however research has determined that it is an autoimmune disease, arising from complex interactions between environmental and genetic influences. There is a latitude incidence variance, with prevalence of MS increased the further one is from the equator; sunlight and vitamin D are therefore being investigated as disease triggers [1, 10, 11, 12]. Childhood exposure to bacteria and viruses have also been investigated, due to a person’s disease risk being set as the incidence of the region they moved to prior to puberty [13, 14]. Of note, every patient with MS have previously been exposed to Epstein–Barr virus (EBV) [15, 16]. Smoking also increases a person’s risk and worsens symptoms following diagnosis [17].
Although the disease is not inherited, it has a genetic component, with those having an affected first degree relative exhibiting an increased incidence of disease [18], and twin studies indicate that there is a 30% chance of developing disease in the second twin if the first has been diagnosed with MS [19]. Genome wide association studies (GWAS) have identified more than 230 genes associated with a person’s MS risk, several being immune genes, particularly those of T cells, B cells, natural killer (NK) cells, monocytes and microglia, implicating involvement of both major branches of the immune system, the innate and adaptive immune responses, in initiation and progression of disease [20, 21, 22, 23]. These studies are supported by several human and animal model functional studies [24, 25, 26].
Cellular toxicity, or the ability to kill other cells, is an important effector mechanisms of the immune system to protect us from infections, cancer or autoimmune diseases. There is a close association between inflammation and neurodegeneration, and cellular toxicity has been implicated as a having a major role in MS [27]. The main players are CD8, or cytotoxic, T cells and NK cells. Cellular toxicity can operate by many mechanisms including NK cell release of lytic granules containing perforin or granzymes to kill directly, or by inducing death receptor-mediated apoptosis via tumour necrosis factor (ligand) superfamily member 10 (TRAIL) or Fas Ligand (FasL) expression on CD8 T cells [28]. There are also antibody-dependent cell-mediated cytotoxic mechanisms (ADCC), where B cells produce antigen specific antibodies or immunoglobulins, that will coat a pathogen or foreign body, marking them for killing or destruction through cell to cell cytoloysis by effector immune cells expressing FcγRIIIA (CD16A), including classical NK cells, monocytes/macrophages, neutrophils, eosinophils, NKT cells, or γδT cells (reviewed in [29]).
The immune system of vertebrates is commonly divided into two main complementary parts, innate and adaptive immunity, the bridge between which is critical for an efficient and effective immune response.
The innate immune system is evolutionary the most primitive, where there is non-specific response to a broad class of antigens. The haematopoietic cells involved include macrophages, dendritic cells, mast cells, neutrophils, eosinophils, NK cells and NKT cells. Although 1908 Nobel Prize winner, Elie Metchnikoff, first described an important role for the innate immune system [30], it is only now being recognised as a critical regulator of human inflammatory disease. Innate immunity involves the recognition of infected cells through surface recognition receptors. These are termed pattern recognition receptors (PRRs) which recognise pathogen associated molecular patterns (PAMPs) unique to non-vertebrate cells, including bacteria and fungi. They are also on internal vesicle membranes for recognition of viral ssRNA and dsRNA and for distinguishing lysed bacterial components [31]. Cytotoxic innate lymphocytes can lyse abnormal or infected cells through the release of cytotoxic granules containing perforin or granzymes, and antigen presenting cells (APCs) can be activated by the innate immune system to present pathogen antigens on their surface. Once activated they will migrate to secondary lymph organs to present their antigen to T cells, and in so doing also activate the adaptive immune system response [32, 33]. The innate immune system therefore functions through a combination of cellular defences and humoral components to defend against nonspecific antigens before activating B and T cells, triggering an adaptive immune response. Speed is the main advantage of innate immunity, with a protective inflammatory response being generated within minutes of pathogen exposure.
Another part of innate immunity is the complement system, which is made up of several small proteins that have been synthesised in the liver and circulate in the blood as active precursors that when stimulated are proteolytically cleaved to release cytokines, leading to a cascade of reactions, ultimately resulting in complement activation or fixation [34]. As the name suggests, they complement or enhance the ability of antibodies and phagocytic cells to clear damaged or diseased cells by promoting inflammation and attack of the cell membrane of the pathogen. Antibodies, generated by the adaptive immune system, can activate the complement system.
Adaptive immunity, sometimes referred to as acquired immunity, is highly specialised and helps to protect the body by recognising antigens, whether they are foreign to the host’s immune system (exogenous), produced by intracellular bacteria or viruses (intracellular) or produced by the host (autoantigen). The adaptive immune system also remembers previously encountered antigens, leading to quicker response times [35]. T and B lymphocytes are the main cells mediating adaptive immunity, with T cells being further divided into the cytotoxic CD8 T cells and CD4 T cells that constitute several classes of what are commonly referred to as “helper T cells”. These cell have produced highly specific receptors for recognition of hundreds or even thousands of antigens through genetic recombination, and this facilitates pathogen specific immunologic effectors pathways, the generation of immunological memory and the regulation of host immune homoeostasis [36].
CD8 T cells recognise infected cells through interaction of T cell receptors with antigens presented by major histocompatibility complex (MHC) class I on the infected cell. The target cell is then killed by the release of cytotoxins, such as perforin and granzymes, from the CD8 T cell [28]. CD4 T cells, on the other hand, recognise antigens presented in the context of MHC II on an APC. Binding to MHC II molecules activates CD4 T cells to release cytokines, which can stimulate CD8 T cells, macrophages and B cells to form an immune response (reviewed in [37]). They can, for example, release cytokines as instructors to CD8 T cells to release cytotoxins, or to B cells to produce pathogen specific antibodies. They therefore instigate and shape adaptive immune responses dependent on the cytokines they release. These can be mainly Th1, or inflammatory, in nature, such as IFN-γ and IL-12, responsible for the control of intracellular pathogens, or polarised to a more anti-inflammatory Th2 response, where cytokines such as IL-4, IL-5 or IL-13 are produced [38, 39]. A disturbance in this Th1/Th2 response can have severe consequences, be they more Th2 in nature, driving asthma and allergy, or Th1 driven, resulting in autoimmune diseases, including MS (reviewed in [40]). A couple of the more recently identified CD4 T cells subsets include Th17 cells that are characterised by production of IL-17 and IL-23, and have been linked to inflammatory diseases, and T regulatory (Treg) cells, which are important in maintaining homeostasis and tolerance of the immune system [41, 42, 43]. Tregs express the transcription factor FoxP3 which is essential for their development and function [44, 45, 46]. In humans, mutations in FOXP3 have been found to result in immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, providing evidence that anomalies of Tregs can cause autoimmune disease and allergy [47].
During production of the T cell receptor (TCR) on T cells and B cell receptor (BCR) on B cells, random genetic recombination events can lead to receptors being produced that are specific to autoantigens [48, 49]. To prevent reaction to self, cells undergo central and peripheral tolerance events through which autoreactive cells are apoptotically removed, first in the primary lymphoid organs of the thymus (T cell) and bone marrow (B cell), and if this fails, in the secondary lymphoid organs after cells migrate to the periphery [49]. Self-reactive antibodies account for 55–75% of all antibodies expressed by early immature B cells, including polyreactive and anti-nuclear specificities [49]. However, it is estimated that the majority of newly produced B cells do not reach maturity, and during central and peripheral tolerance most of the self-reactive B cells are removed. If both selection processes fail in T or B cells, this will result in T and B cells able to react with the body’s own cells and tissues. These events lead to autoimmune disease.
Inflammation as a response of the body to infection or cell injury is a well-known concept that dates back to the beginning of medicine. However, Metchnikoff pointed out that although normally a method of protection, inflammation that exceeds normal bounds can cause disease [27]. Even with this knowledge, it was not until the 1950s that inflammation was recognised as inducing an autoimmune reaction responsible for disease. Autoimmune disease is characterised by an excessive immune response against self, often resulting in inflammation and tissue destruction, in the absence of a threat to the organism [50, 51]. Aberrant immune responses have been associated with over 80 disorders, including multiple sclerosis, and affects 5–7% of the population [52]. Clinical observations over the past decade have suggested that the prevalence of all autoimmune disease, not just MS, is increasing, bringing the issue to the forefront of scientific interest [53, 54]. Successful treatment of autoimmune disease is also of great societal interest, as they are commonly characterised by chronic natures, ongoing health care costs, and debilitating issues resulting in loss of productivity.
Immunological self-tolerance is maintained in part by Tregs. Tregs are CD4 T cells that actively and dominantly supress lymphocytes, particularly self-reactive T cells in the normal periphery that exist despite the deletion mechanisms in the thymus [43]. Natural CD25+ CD4 Tregs utilise several modes of suppression, including cell contact dependent mechanisms, such as the killing of APCs or responder T cells by granzyme and perforin, and by mediation of soluble factors, such as the secretion of immunosuppressive cytokines like IL-10, TGF-β or IL-35, or deprivation of cytokines necessary for expansion and survival of responder T cells (reviewed in [55, 56]).
Optimal T cell function relies on a carefully maintained state of equilibrium. When one subpopulation of T helper cells is activated, others are modulated or inhibited to promote the most specific effector response to the threat [57]. The cellular development of Tregs shares a common cytokine with Th17 cells, TGF-β [41, 42]. Th17 cells are the opposing force to Tregs, serving as an effector lymphocyte population that plays a key role in autoimmunity [41, 42]. At homeostasis, Th17 cells promote gut barrier defence, granulopoiesis, granulocyte chemotaxis and immunity against extracellular pathogen [58]. IL-17 induces granulopoesis indirectly through the stimulation of fibroblasts, epithelial and endothelial cells to secrete GM-CSF, IL-6, IL-8 and MIP-2, with IL-8 and MIP-2 enhancing chemotaxis of neutrophils [59, 60]. While Th17 cell mediated immunity is crucial for maintaining mucosal and haematopoietic homeostasis, too strong a response can induce autoimmunity. The relationship between Tregs and effector Th17 must remain balanced to provide the optimal functional immunity and health of an organism.
Another theory of immune regulation is the hypothesis of homeostasis between Th1 and Th2 cells. The subpopulations can be distinguished by the cytokines they produce and the expression of difference cell surface molecules. Th1 cells are responsible for cell mediated immunity, phagocyte dependent protective responses, B cell activation and production of opsonising antibodies such as IgG1, whereas Th2 cells produce cytokines that are responsible for strong antibody production, eosinophil activation and inhibition of several macrophage functions, thus providing phagocyte independent protective responses [61]. Th2 cells are also responsible for the general activation of B cells. When the Th1/Th2 paradigm is thrown out of balance by failure of central or peripheral tolerance, immunological disorders can occur due to uncontrolled responses [61].
MS arises when there is an imbalance in the body’s immune response, shifting it from a beneficial immune process that fights infection and disease towards a self-aggressive immune attack on the cells within the CNS (Figure 1). Genetic and environmental factor interaction may facilitate movement of autoreactive T cells, macrophages and NK cells and demyelinating antibodies from the periphery to the CNS. In the periphery self-antigens can be presented on MHC II molecules by APCs to TCRs on T cells, thereby activating proinflammatory T cells [48]. The activated T cells can then migrate through the blood brain barrier to the brain and spinal cord [2]. Once in the CNS the T cells can be reactivated by CNS antigens presented on MHC II by other APCs, primarily microglial cells [62]. Secretion of proinflammatory Th1 cytokines by the reactivated T cells can induce CNS inflammation by activating macrophages, B cells and other T cells [63]. The antibodies can also initiate a complement cascade resulting in assembly of the membrane attack complex, forming pores in the myelin membranes.
Multiple sclerosis pathogenesis. Autoreactive T cells, macrophages and NK cells, and demyelinating antibodies, may migrate across a compromised blood brain barrier. T cells are reactivated in the central nervous system by antigen presenting cells (APC). Anti-inflammatory cytokines released by Th2 cells can stimulate B cells to differentiate into plasma cells that secrete demyelinating antibodies. Alternatively, the release of proinflammatory cytokines by Th1 cells can enhance immune response, via activation of other immune cells such as CD8 T cells and macrophages to attack the myelin sheath and oligodendrocytes causing demyelination and the development of clinical symptoms of MS (created with
While inflammation and neurodegeneration are correlated in active lesions, research suggests that neurodegeneration may become independent from inflammation in progressive disease [64]. There are many MS therapeutics that suppress proinflammatory cytokines or their effector functions, but not all treatments show equal efficacy and can cause unintended effects. Currently, there is no cure. It is thus becoming clear that there is a need to elucidate the different populations important in initiating and progressing disease, and by studying their interactive networks, identify possible areas for targeted intervention.
While there is overwhelming evidence of a role for T cells in the pathogenesis of MS, further studies in humans and in the mouse model of disease, experimental autoimmune encephalomyelitis (EAE), provides compelling evidence that other cell types play major roles. Linkage to the Human Leukocyte antigen (HLA) locus, including MHC I and II genes, was the first genetic locus identified, and still provides today the strongest linkage to MS. Further studies have identified an extended HLA haplotype, HLA-DRB1*15:01, DQA1*0102, DQB1*0602, within the MHC class II region [65]. As MHC II molecules specifically present peptide antigens to activate CD4 T cells, this suggests that CD4 T cells are important in initiation and progression of MS.
Th1 cells are a lineage of CD4 effector T cells that promote cell mediated immune responses and are necessary for defence against intracellular viral and bacterial pathogens. They were originally believed to be the main pathogenic T cells in MS, not only because susceptibility genes were linked to MHC II molecules, but also because immune surveillance of a healthy brain to scan for infection, showed favouring towards infiltration by Th1 cells, and therapeutic strategies designed to induce a shift from Th1 to Th2 immune response resulted in beneficial outcomes in MS patients [66, 67, 68].
The development of Th1 cells is coupled to the involvement of cell-extrinsic and cell-intrinsic factors, including signal transducer activator 1 (STAT1), the transcription factor Tbx21, IL-21 and STAT4 [69]. The CD4-Th1 model for MS was further supported by a trial performed in 1987, which found that administering IFN-γ to RRMS patients exacerbated disease. An accompanying increase in circulating monocytes bearing class II (HLA-DR) surface antigens suggested that the attacks induced by the treatment were immunologically mediated [70].
Th1 cells are also known to drive EAE. However, it was found that transgenic mice that lacked Th1 cells developed more severe EAE, thereby contradicting the Th1 cell theory for MS [71]. This conundrum was partially resolved following further investigation involving IL-23, a heterodimer cytokine composed of a unique p19 subunit and a common p40 subunit shared with IL-12. IL-23 promotes development of Th17 cells as opposed to Th1 cells [72]. Early studies on Th17 cells therefore dismissed a role for the previously favoured Th1 cells, but more recent research suggests that both cell types may play distinct roles in pathology [73]. It was suggested that Th1 cells accessed the CNS initially and subsequently facilitated the recruitment of Th17 cells [73].
Analysis of CNS tissue revealed distinct histopathological features and immune profiles depending on cytokine modulated T cells. IL-12p70 driven disease was characterised by macrophage-rich infiltrates, however in IL-23 driven lesions it was found that neutrophils and the growth factor, granulocyte colony stimulating factor (CSF), were the most prominent [74]. Research has shown that while IL-23 is commonly associated with the expansion of Th17 cells or the stabilisation of the Th17 phenotype, a similar course of EAE has been reported following the transfer of MOG-specific T cells into either wild type or IL-23 knockout mice [75]. This suggests that once encephalitogenic cells have been generated, EAE can develop in the absence of IL-23. IL-23 may therefore only be necessary for disease induction and not the effector phase of disease.
While MHC II molecules were found to be the strongest associated with MS in genetic studies, the MHC I HLA-A*0301 allele, independent of the HLA II haplotype DRB1*15,DQB1*06, was found to be increased in MS patients [65]. There was also a negative association with the MHC I HLA-A*0201 and disease [76]. As MHC I molecules are recognised by CD8 T cells, this suggests that CD8 T cells play a role in MS.
In one of the first studies that shifted from a CD4 T cell focus, CD8 T cells outnumbered the CD4 T cell subset in all parenchyma samples from MS patients, regardless of the MS type, duration or speed of disease progression [77]. Research has also shown that APCs, including dendritic cells (DCs), interact with T cells and proliferating lymphocytes, predominately CD8 T cells, at the margins of chronic active MS lesions [78]. CD8 T cells have also been found within active lesions of RRMS patients [77]. These T cells, and to a lesser extent, compartmentally differentially distributed B cells, have been shown to correlate with disease progression and damage.
CD8 T cells are an important subpopulation of MHC I restricted T cells, and are mediators of adaptive immunity. Cytotoxic T cells specialise in direct killing of cells that are infected, particularly with viruses, or are cancerous or damaged in other ways. Cytotoxic cells rely on two mechanisms for lytic activity: granule-dependent cytotoxicity (reviewed in [79]) and death receptor dependent cytotoxicity (reviewed in [80]). The principle mechanism used is granule-dependent cytotoxicity. In lesion prone areas of the CNS, T lymphocytes, including CD8 cytotoxic T lymphocytes (CTLs), are recruited to the affected tissue and brain cells are stimulated to present antigens to the T lymphocytes via de novo expression of MHC molecules. Although levels of MHC I and MHC II are very low in normal CNS parenchyma, neural injury leads to a massive increase in activated and phagocytotic microglial, which can serve as competent APCs [81]. To develop into functioning CD8 T cells, the TCR must recognise the MHC-peptide combination along with the costimulatory signal from APCs. While classical MHC I molecules necessary for CD8 T cell activation are not usually expressed on neural cells, they are induced in most inflammatory and degenerative CNS diseases [82].
Oligodendrocytes lack expression of costimulatory molecules and are thus unable to trigger the full effector of T cells, however they have been known to express MHC I in vitro [83]. Therefore, despite the lack of complete activation of the T cells, oligodendrocytes may still be targets of primed CTLs. MHC I expressing oligodendrocytes are susceptible to lysis by blood donor derived CD8 CTLs [83]. IFN-γ treated human oligodendrocytes also express Fas/CD95, and are therefore susceptible to death receptor dependent cytotoxicity [84]. Another component of the CNS, the neurons, were found to be capable of expressing MHC I when treated with IFN-γ [85, 86]. Medana and colleagues in 2000 discovered that hippocampal neurons were highly susceptible to direct application of cytotoxic granules, but showed no signs of perforin mediated lysis or membrane damage following attack by CTLs [87]. This effect was not observed in any other cell type.
Research to date indicates that all cellular elements of the CNS may act as targets to CTLs but that susceptibility and cytotoxic pathways involved vary dependent on the cell type and the immune activations during the course of the inflammatory process.
Historically, B cells have not been recognised as major players in regulatory function in the development of autoimmune diseases, although the identification of autoantibodies produced by autoreactive plasma cells and their pathogenic consequences are widely accepted [88]. B cells are considered effector cells as well as cells with immunoregulatory potential. B cells in MS patients express increased levels of costimulatory molecules, increasing the stimulation of antigen-reactive T cells [89]. It has been reported that MS patients have increased levels of IL-6 and GM-CSF, correlating with increased Th17 cells [90, 91]. B cell targeted therapies utilise B cell depleting monoclonal antibodies against the B cell marker CD20. These antibodies trigger B cell lysis through antibody dependent cellular cytotoxicity, complement dependent cytotoxicity or apoptosis induction [92].
Administration of daclizumab, an alpha subunit of IL-2 receptor blocking monoclonal antibody, to MS patients was found to strongly reduce brain inflammation. This therapy, while being associated with a decline in circulating CD4 and CD8 T cells, also correlated with a significant expansion of CD56bright NK cells in vivo. This provided supporting evidence of NK cell-mediated negative immunoregulation of T cells during daclizumab treatment [93], and the identification of NK cells in association with MS, where positive outcome was possibly due to the treatment’s effect of increasing the NK cell numbers [94, 95].
For decades, NK cells have been classified as a component of the innate immune system. However, evidence suggests that, like B and T cells, NK cells are educated during development, possess antigen-specific receptors, undergo clonal expansion and generate memory cells (reviewed in [96]). Research originally suggested that NK cells developed and underwent differentiation within the bone marrow, however more recent extensive ex vivo characterisation of haematopoietic precursor cells (HPCs) and downstream NK cell development intermediates (NKDIs) reveals that they are enriched in secondary lymphoid tissues (STLs), including the tonsils, spleen and lymph nodes [97, 98, 99, 100]. This suggests that NK cells in humans can differentiate in the SLTs, and may do so preferentially.
Human NK cells are phenotypically defined by expression of CD56 and the lack of CD3 expression [101]. CD56 is the 140-kDa isoform of neural cell adhesion molecule (NCAM) found on NK cells and a minority of T cells [102]. NK cells are categorised into two distinct populations depending on the cell surface density of CD56. The majority of human NK cells, approximately 90%, express low levels of CD56 (CD56dim) and high levels of FCyRIII (CD16), while the minority express higher levels of CD56 (CD56bright) [103]. CD56bright NK cells have long being associated with an immunoregulatory role, due to increased production of NK-derived immunoregulatory cytokines, including IFN-γ, TNF-β, IL-10, IL-13 and GM-CSF, and reduced cytotoxicity compared to CD56dim NK cells [104]. CD56bright NK cells express receptors for cytokines such as IL-12, IL-15 and IL-18, produced by APCs, which can trigger proliferation of CD56bright NK cells and their production of molecules, including IFN-γ, IL-10 and IL-13 [104]. It has been demonstrated that DCs are a key source of cytokines for the activation of CD56bright NK cells [105]. Modulation and proliferation of CD56bright NK cells can also occur due to DC-derived IL-27 [105]. Activated NK cells can modulate the function of APCs by stimulating monocytes to produce TNF-α and kill immature DCs by a perforin-dependent process referred to as DC editing [106, 107].
However, more recent research has challenged this commonly accepted concept of CD56bright as the primary source of immunoregulatory cytokines. Studies have shown that CD56dim NK cells are also a major source of proinflammatory cytokines and chemokines that are induced rapidly after target cell recognition [108, 109].
The absence of MHC class I molecules, as indicated by virally infected cells or cancerous cells with MHC I downregulated, is not always sufficient to induce NK cell mediated death, suggesting that there must be activating receptors on NK cells whose affinity for target cell ligands dominates over the inhibitory signals of the NK cell. Some activating receptors identified include NKG2D, the NCR, and NKp80 [110, 111, 112]. NKG2D is the best characterised of these activating NK cell receptors. It is a c-type lectin-like receptor expressed on the surface of all human NK cells and recognises at least six ligands, each with a MHC class I homology [113]. Following receptor-ligand interaction, NKG2D phosphorylates an adaptor protein that recruits and activates phosphatidylinositol-3 (PI-3) kinase, which results in perforin-dependent cytotoxicity [114, 115]. Gunesh et al. found that the deletion of CD56 on the NK92 cell line lead to impaired cytotoxic function. The knockout CD56 cells failed to polarise during immunological synapse formation and had severely impaired exocytosis of lytic granules [116].
Treatment of MS patients with IFN-β caused an expansion of CD56bright NK cells, and resulted in the population of CD56dim cells being diminished [117]. The study also found that the proportion of CD56bright NK cells was significantly higher in the secondary lymphoid tissues compared to the peripheral blood for the control group [117]. This suggested that CD56bright NK cells may preferably locate within secondary lymphoid tissues, where they are able to interact with T cells and contribute to control of disease activity in MS [117].
There is an ongoing debate as to whether NK cells have a predominately beneficial or detrimental role in EAE, made even more complex by the lack of CD56 expression on murine NK cells. Studies have shown that enhancing the regulatory features of NK cells ameliorates the disease course of EAE. When the interaction between NKG2A and its ligand Qa-1 (the murine equivalent to the human HLA-E) expressed on target cells were blocked by antibodies specific for either antigen, it was found that NKG2A-expressing NK cells in particular decreased CNS inflammation by killing microglial and T cells [118, 119].
Enrichment of NK cells through treatment with IL-2 coupled with a monoclonal antibody specific for IL-2 (IL-2 mAb) was also found to ameliorate EAE [120]. The IL-2 mAb supplements the proliferation of NK and CD8 T cells in mice by increasing the biological activity of the pre-existing IL-2 by formation of immune complexes [121]. Increased levels of IL-2 was also found to expand Tregs while preventing the induction of Th17 during EAE development [122]. However, NK cells have different effects during the early stages of EAE, and possibly MS, compared to the late stages. In the early stages NK cells were found to protect the CNS whereas NK cells were found to kill neural stem cells (NSCs) during the late stages of EAE, as a result of reduced expression of Qa-1 on NSCs [120, 123].
NKT cells are unique T lymphocytes that express NK cell lineage markers, and act as a bridge between the innate and adaptive immune system. NKT cells account for a small percentage of lymphocytes, but have profound immunomodulatory roles in a variety of diseases [124]. There are two categories of NKT cells, type I and type II. Type I NKT cells, also known as invariant NKT cells (iNKT cells), express a semi-invariant Vα24-Jα18 (Vα14-Jα18 in mice), paired with a restricted range of β chains, that recognises α-galactosylceramide (α-GalCer) presented by CD1d [125, 126]. Type II NKT cells use TCRα and β chains that are reactive to a broad range of antigens, but do not recognise α-Galcer [127].
Nonobese diabetic (NOD) mice are susceptible to MOG-induced EAE. However, if NKT cells are increased either by transgenesis or adoptive transfer, the mice show protection from disease [128]. EAE protection has been correlated with inhibition of Ag-specific IFN-γ production in the spleen, modulating the encephalitogenic Th1 response [128]. There is conflicting evidence as to the effects of deletion of NKT cells on EAE. Some studies resulted in no effect on disease[129], with other studies showing disease exacerbation in CD1d-deficient and Jα18-deficient mice [130, 131]. Activation of type I NKT cells by α-GalCer has been shown to improve EAE outcome. These improvements arise by indirectly enhancing Th2 response and reducing the Th1 response, or potentiating the differential of immunosuppressive myeloid cells [131, 132, 133, 134]. However conflicting studies showed that high doses of α-GalCer could worsen EAE by directly enhancing Th17 and Th1 differentiation through phosphorylation of STAT3 and activation of NK-κB [135].
NKT cells from MS patients have been reported to have an increased production of cytokines. IL-4 production was increased by CD4 NKT cell clones in RRMS compared to other MS progression types, causing significant Th2 bias [136]. However, NKT cells in progressive MS patients displayed proinflammatory profiles [137]. It has also been suggested that the current available drugs for MS treatment may function through NKT cell targeting. A large reduction of type I NKT cells in peripheral blood was associated with remission of MS [136]. Type 1 interferon-β (T1IFN-β), a popular disease modifying therapy (DMT) for RRMS treatment, has been noted to promote expansion and functionality of type I NKT cells in vitro and to prevent disease in in vivo models of MS [138]. Research indicates a diverse role for NKT cells in MS pathology due to cytokine production.
Besides imbalances in cytokine levels in the CNS and cerebrospinal fluid (CSF), immune imbalances also occur in the blood of MS patients, as reflected by altered levels of cytokines and cytokine producing cells (reviewed in [139]). The cause of these imbalances are thought to be due to circulating monocytes, with monocytes and macrophages influencing early MS, mediating both pro and anti-inflammatory responses [140, 141].
Surface expression of CD14 and CD16 are used to distinguish three distinct monocyte subsets: classical (CD14++CD16−), intermediate (CD14++CD16+) and nonclassical (CD14+ CD16++) [142]. Monocytes and macrophages perform the key functions of antigen presentation and co-stimulation vital to the body’s immune response, with important roles in T and B cell activation and differentiation via the CD40-CD154 interaction (reviewed in [143]). Macrophages are primarily derived from blood borne monocytes, are present at sites of active demyelination in MS, and are assumed to be a part of the demyelinating process [144]. These inflammatory cells produce a range of toxic oxygen metabolites which mediate host tissue destruction. During MS progression, there is a significant expansion of the CD16+ monocyte population, which can primarily be attributed to nonclassical monocytes [145]. Depletion of these nonclassical monocytes may be an alternative to T and B cell depletion with the advantage of leaving the major classical monocyte population untouched. Selective subset depletion of monocytes may also supplement existing therapies to increase efficacy [145].
Multiple sclerosis is a complex autoimmune disease. Due to the many cell types involved in pathogenesis of the disease, therapeutics and treatments are often broad ranged and relatively inefficient. Further studies are necessary to uncover the genetic and environmental triggers leading to aberrant cellular toxicity and its role in MS pathogenesis. Discovering these and the related pathways will potentially lead to more targeted therapeutics and the elimination of not only MS but other autoimmune and neurological diseases in the future.
AMLW is supported by an Australian Government Research Training Program Stipend and MAJ was supported by an MS Research Australia/NHMRC Research Betty Cuthbert Fellowship. Project funds were obtained from Multiple Sclerosis Research Australia (MSRA), Lions’ club, Australia, and Australian Health Research Alliance-Women’s Health Research Translation Network (WHRTN).
The authors declare no conflict of interest.
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Over the past few decades, no major new types of antibiotics have been produced and almost all known antibiotics are increasingly losing their activity against pathogenic microorganisms. The levels of multi-drug resistant bacteria have also increased. It is known that worldwide, more than 60% of all antibiotics that are produced find their use in animal production for both therapeutic and non-therapeutic purposes. The use of antimicrobial agents in animal husbandry has been linked to the development and spread of resistant bacteria. Poultry products are among the highest consumed products worldwide but a lot of essential antibiotics are employed during poultry production in several countries; threatening the safety of such products (through antimicrobial residues) and the increased possibility of development and spread of microbial resistance in poultry settings. This chapter documents some of the studies on antibiotic usage in poultry farming; with specific focus on some selected bacterial species, their economic importance to poultry farming and reports of resistances of isolated species from poultry settings (farms and poultry products) to essential antibiotics.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Christian Agyare, Vivian Etsiapa Boamah, Crystal Ngofi Zumbi and\nFrank Boateng Osei",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"261271",title:"MSc.",name:"Crystal Ngofi",middleName:null,surname:"Zumbi",slug:"crystal-ngofi-zumbi",fullName:"Crystal Ngofi Zumbi"},{id:"261272",title:"MSc.",name:"Frank Boateng",middleName:null,surname:"Osei",slug:"frank-boateng-osei",fullName:"Frank Boateng Osei"},{id:"261273",title:"Dr.",name:"Vivian Etsiapa",middleName:null,surname:"Boamah",slug:"vivian-etsiapa-boamah",fullName:"Vivian Etsiapa Boamah"}]},{id:"49246",doi:"10.5772/61300",title:"Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers",slug:"chitosan-as-a-biomaterial-structure-properties-and-electrospun-nanofibers",totalDownloads:4727,totalCrossrefCites:27,totalDimensionsCites:63,abstract:"Chitosan is a polysaccharide derived from chitin; chitin is the second most abundant polysaccharide in the world, after cellulose. Chitosan is biocompatible, biodegradable and non-toxic, so that it can be usedin medicalapplications such as antimicrobial and wound healing biomaterials. It also used as chelating agent due to its ability to bind with cholesterol, fats, proteins and metal ions.",book:{id:"4648",slug:"concepts-compounds-and-the-alternatives-of-antibacterials",title:"Concepts, Compounds and the Alternatives of Antibacterials",fullTitle:"Concepts, Compounds and the Alternatives of Antibacterials"},signatures:"H. M. Ibrahim and E.M.R. El- Zairy",authors:[{id:"90645",title:"Dr.",name:"Hassan",middleName:null,surname:"Ibrahim",slug:"hassan-ibrahim",fullName:"Hassan Ibrahim"},{id:"175694",title:"Dr.",name:"Enas",middleName:null,surname:"El- Zairy",slug:"enas-el-zairy",fullName:"Enas El- Zairy"}]},{id:"70919",doi:"10.5772/intechopen.90891",title:"Antimicrobial Effect of Titanium Dioxide Nanoparticles",slug:"antimicrobial-effect-of-titanium-dioxide-nanoparticles",totalDownloads:1817,totalCrossrefCites:21,totalDimensionsCites:47,abstract:"The widespread use of antibiotics has led to the emergence of multidrug-resistant bacterial strains, and therefore a current concern for food safety and human health. The interest for new antimicrobial substances has been focused toward metal oxide nanoparticles. Specifically, titanium dioxide (TiO2) has been considered as an attractive antimicrobial compound due to its photocatalytic nature and because it is a chemically stable, non-toxic, inexpensive, and Generally Recognized as Safe (GRAS) substance. Several studies have revealed this metal oxide demonstrates excellent antifungal and antibacterial properties against a broad range of both Gram-positive and Gram-negative bacteria. These properties were significantly improved by titanium dioxide nanoparticles (TiO2 NPs) synthesis. In this chapter, latest developments on routes of synthesis of TiO2 NPs and antimicrobial activity of these nanostructures are presented. Furthermore, TiO2 NPs favor the inactivation of microorganisms due to their strong oxidizing power by free radical generation, such as hydroxyl and superoxide anion radicals, showing reductions growth against several microorganisms, such as Escherichia coli and Staphylococcus aureus. Understanding the main mechanisms of antimicrobial action of these nanoparticles was the second main purpose of this chapter.",book:{id:"9521",slug:"antimicrobial-resistance-a-one-health-perspective",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A One Health Perspective"},signatures:"Carol López de Dicastillo, Matias Guerrero Correa, Fernanda B. Martínez, Camilo Streitt and Maria José Galotto",authors:[{id:"244902",title:"Dr.",name:"Carol",middleName:null,surname:"Lopez De Dicastillo",slug:"carol-lopez-de-dicastillo",fullName:"Carol Lopez De Dicastillo"},{id:"315494",title:"Mr.",name:"Matias",middleName:null,surname:"Guerrero Correa",slug:"matias-guerrero-correa",fullName:"Matias Guerrero Correa"},{id:"315495",title:"Ms.",name:"Fernanda",middleName:null,surname:"B. Martínez",slug:"fernanda-b.-martinez",fullName:"Fernanda B. Martínez"},{id:"315496",title:"Mr.",name:"Camilo",middleName:null,surname:"Zuñiga",slug:"camilo-zuniga",fullName:"Camilo Zuñiga"},{id:"315497",title:"Dr.",name:"Maria José",middleName:null,surname:"Galotto",slug:"maria-jose-galotto",fullName:"Maria José Galotto"}]},{id:"65613",doi:"10.5772/intechopen.84411",title:"The Methods for Detection of Biofilm and Screening Antibiofilm Activity of Agents",slug:"the-methods-for-detection-of-biofilm-and-screening-antibiofilm-activity-of-agents",totalDownloads:9283,totalCrossrefCites:15,totalDimensionsCites:26,abstract:"Biofilm producer microorganisms cause nosocomial and recurrent infections. Biofilm that is a sticky exopolysaccharide is the main virulence factor causing biofilm-related infections. Biofilm formation begins with attachment of bacteria to biotic surface such as host cell or abiotic surface such as prosthetic devices. After attachment, aggregation of bacteria is started by cell-cell adhesion. Aggregation continues with the maturation of biofilm. Dispersion is started by certain conditions such as phenol-soluble modulins (PSMs). By this way, sessile bacteria turn back into planktonic form. Bacteria embedded in biofilm (sessile form) are more resistant to antimicrobials than planktonic bacteria. So it is hard to treat biofilm-embedded bacteria than planktonic forms. For this reason, it is important to detect biofilm. There are a few biofilm detection and biofilm production methods on prosthetics, methods for screening antibacterial effect of agents against biofilm-embedded microorganism and antibiofilm effect of agents against biofilm production and mature biofilm. The aim of this chapter is to overview direct and indirect methods such as microscopy, fluorescent in situ hybridization, and Congo red agar, tube method, microtiter plate assay, checkerboard assay, plate counting, polymerase chain reaction, mass spectrometry, MALDI-TOF, and biological assays used by antibiofilm researches.",book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}]},{id:"63397",doi:"10.5772/intechopen.80624",title:"Antibiotic Resistance in Lactic Acid Bacteria",slug:"antibiotic-resistance-in-lactic-acid-bacteria",totalDownloads:2486,totalCrossrefCites:12,totalDimensionsCites:21,abstract:"Most starter cultures belong to the lactic acid bacteria group (LAB) and recognized as safe by the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA). However, LAB may act as intrinsic or extrinsic reservoirs for antibiotic resistance (AR) genes. This fact may not constitute a safety concern itself, as the resistance gene transfer is vertical. Nevertheless, external genetic elements may induce changes that favor the horizontal transfer transmission of resistance from pathogens as well as from the human intestinal microbiota, which represents a severe safety issue. Some genus of AR LAB includes Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, and Streptococcus isolated from fermented meat and milk products. Currently, the WHO recommends that LAB used in the food industry should be free of resistance. Therefore, the objective of this chapter is to present an overview of the LAB antibiotic resistance and some methods to determine the same.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Yenizey M. Álvarez-Cisneros and Edith Ponce-Alquicira",authors:[{id:"256345",title:"Dr.",name:"Yenizey Merit",middleName:null,surname:"Alvarez Cisneros",slug:"yenizey-merit-alvarez-cisneros",fullName:"Yenizey Merit Alvarez Cisneros"},{id:"256347",title:"Dr.",name:"Edith",middleName:null,surname:"Ponce-Alquicira",slug:"edith-ponce-alquicira",fullName:"Edith Ponce-Alquicira"}]}],mostDownloadedChaptersLast30Days:[{id:"65613",title:"The Methods for Detection of Biofilm and Screening Antibiofilm Activity of Agents",slug:"the-methods-for-detection-of-biofilm-and-screening-antibiofilm-activity-of-agents",totalDownloads:9277,totalCrossrefCites:15,totalDimensionsCites:26,abstract:"Biofilm producer microorganisms cause nosocomial and recurrent infections. Biofilm that is a sticky exopolysaccharide is the main virulence factor causing biofilm-related infections. Biofilm formation begins with attachment of bacteria to biotic surface such as host cell or abiotic surface such as prosthetic devices. After attachment, aggregation of bacteria is started by cell-cell adhesion. Aggregation continues with the maturation of biofilm. Dispersion is started by certain conditions such as phenol-soluble modulins (PSMs). By this way, sessile bacteria turn back into planktonic form. Bacteria embedded in biofilm (sessile form) are more resistant to antimicrobials than planktonic bacteria. So it is hard to treat biofilm-embedded bacteria than planktonic forms. For this reason, it is important to detect biofilm. There are a few biofilm detection and biofilm production methods on prosthetics, methods for screening antibacterial effect of agents against biofilm-embedded microorganism and antibiofilm effect of agents against biofilm production and mature biofilm. The aim of this chapter is to overview direct and indirect methods such as microscopy, fluorescent in situ hybridization, and Congo red agar, tube method, microtiter plate assay, checkerboard assay, plate counting, polymerase chain reaction, mass spectrometry, MALDI-TOF, and biological assays used by antibiofilm researches.",book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}]},{id:"62553",title:"Antibiotic Use in Poultry Production and Its Effects on Bacterial Resistance",slug:"antibiotic-use-in-poultry-production-and-its-effects-on-bacterial-resistance",totalDownloads:7327,totalCrossrefCites:43,totalDimensionsCites:92,abstract:"A surge in the development and spread of antibiotic resistance has become a major cause for concern. Over the past few decades, no major new types of antibiotics have been produced and almost all known antibiotics are increasingly losing their activity against pathogenic microorganisms. The levels of multi-drug resistant bacteria have also increased. It is known that worldwide, more than 60% of all antibiotics that are produced find their use in animal production for both therapeutic and non-therapeutic purposes. The use of antimicrobial agents in animal husbandry has been linked to the development and spread of resistant bacteria. Poultry products are among the highest consumed products worldwide but a lot of essential antibiotics are employed during poultry production in several countries; threatening the safety of such products (through antimicrobial residues) and the increased possibility of development and spread of microbial resistance in poultry settings. This chapter documents some of the studies on antibiotic usage in poultry farming; with specific focus on some selected bacterial species, their economic importance to poultry farming and reports of resistances of isolated species from poultry settings (farms and poultry products) to essential antibiotics.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Christian Agyare, Vivian Etsiapa Boamah, Crystal Ngofi Zumbi and\nFrank Boateng Osei",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"261271",title:"MSc.",name:"Crystal Ngofi",middleName:null,surname:"Zumbi",slug:"crystal-ngofi-zumbi",fullName:"Crystal Ngofi Zumbi"},{id:"261272",title:"MSc.",name:"Frank Boateng",middleName:null,surname:"Osei",slug:"frank-boateng-osei",fullName:"Frank Boateng Osei"},{id:"261273",title:"Dr.",name:"Vivian Etsiapa",middleName:null,surname:"Boamah",slug:"vivian-etsiapa-boamah",fullName:"Vivian Etsiapa Boamah"}]},{id:"65914",title:"Introductory Chapter: The Action Mechanisms of Antibiotics and Antibiotic Resistance",slug:"introductory-chapter-the-action-mechanisms-of-antibiotics-and-antibiotic-resistance",totalDownloads:4428,totalCrossrefCites:6,totalDimensionsCites:10,abstract:null,book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu, Nesrin Gareayaghi and Bekir S. Kocazeybek",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"},{id:"248288",title:"Prof.",name:"Bekir",middleName:null,surname:"Kocazeybek",slug:"bekir-kocazeybek",fullName:"Bekir Kocazeybek"},{id:"406463",title:"Dr.",name:"Nesrin",middleName:null,surname:"Gareayaghi",slug:"nesrin-gareayaghi",fullName:"Nesrin Gareayaghi"}]},{id:"63397",title:"Antibiotic Resistance in Lactic Acid Bacteria",slug:"antibiotic-resistance-in-lactic-acid-bacteria",totalDownloads:2486,totalCrossrefCites:12,totalDimensionsCites:21,abstract:"Most starter cultures belong to the lactic acid bacteria group (LAB) and recognized as safe by the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA). However, LAB may act as intrinsic or extrinsic reservoirs for antibiotic resistance (AR) genes. This fact may not constitute a safety concern itself, as the resistance gene transfer is vertical. Nevertheless, external genetic elements may induce changes that favor the horizontal transfer transmission of resistance from pathogens as well as from the human intestinal microbiota, which represents a severe safety issue. Some genus of AR LAB includes Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, and Streptococcus isolated from fermented meat and milk products. Currently, the WHO recommends that LAB used in the food industry should be free of resistance. Therefore, the objective of this chapter is to present an overview of the LAB antibiotic resistance and some methods to determine the same.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Yenizey M. Álvarez-Cisneros and Edith Ponce-Alquicira",authors:[{id:"256345",title:"Dr.",name:"Yenizey Merit",middleName:null,surname:"Alvarez Cisneros",slug:"yenizey-merit-alvarez-cisneros",fullName:"Yenizey Merit Alvarez Cisneros"},{id:"256347",title:"Dr.",name:"Edith",middleName:null,surname:"Ponce-Alquicira",slug:"edith-ponce-alquicira",fullName:"Edith Ponce-Alquicira"}]},{id:"49246",title:"Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers",slug:"chitosan-as-a-biomaterial-structure-properties-and-electrospun-nanofibers",totalDownloads:4726,totalCrossrefCites:27,totalDimensionsCites:63,abstract:"Chitosan is a polysaccharide derived from chitin; chitin is the second most abundant polysaccharide in the world, after cellulose. Chitosan is biocompatible, biodegradable and non-toxic, so that it can be usedin medicalapplications such as antimicrobial and wound healing biomaterials. It also used as chelating agent due to its ability to bind with cholesterol, fats, proteins and metal ions.",book:{id:"4648",slug:"concepts-compounds-and-the-alternatives-of-antibacterials",title:"Concepts, Compounds and the Alternatives of Antibacterials",fullTitle:"Concepts, Compounds and the Alternatives of Antibacterials"},signatures:"H. M. Ibrahim and E.M.R. El- Zairy",authors:[{id:"90645",title:"Dr.",name:"Hassan",middleName:null,surname:"Ibrahim",slug:"hassan-ibrahim",fullName:"Hassan Ibrahim"},{id:"175694",title:"Dr.",name:"Enas",middleName:null,surname:"El- Zairy",slug:"enas-el-zairy",fullName:"Enas El- Zairy"}]}],onlineFirstChaptersFilter:{topicId:"897",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81704",title:"Quorum Sensing Inhibition Based Drugs to Conquer Antimicrobial Resistance",slug:"quorum-sensing-inhibition-based-drugs-to-conquer-antimicrobial-resistance",totalDownloads:22,totalDimensionsCites:0,doi:"10.5772/intechopen.104125",abstract:"Quorum sensing is the cell to cell communication mechanism in microorganism through signalling molecules. Regulation of virulence factor, sporulation, proteolytic enzymes production, biofilm formation, auto-inducers, cell population density are key physiological process mediated through quorum-sensing (QS) signalling. Elevation of innate immune system and antibiotic tolerance of pathogens is highly increased with perspective of quorum-sensing (QS) activity. Development of novel drugs is highly attractive scenario against cell-cell communication of microbes. Design of synthetic drugs and natural compounds against QS signal molecules is vital combat system to attenuate microbial pathogenicity. Quorum sensing inhibitors (QSIs), quorum quenchers (QQs), efflux pump inhibitors (EPIs) act against multi-drug resistance strains (MDR) and other pathogenic microbes through regulation of auto-inducers and signal molecule with perceptive to growth arrest both in-vitro and in-vivo. QQs, QSIs and EPIs compounds has been validated with various animal models for high selection pressure on therapeutics arsenal against microbe’s growth inhibition. Promising QSI are phytochemicals and secondary metabolites includes polyacetylenes, alkaloids, polyphenols, terpenoids, quinones.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Kothandapani Sundar, Ramachandira Prabu and Gopal Jayalakshmi"},{id:"82372",title:"Unlocking the Potential of Ghost Probiotics in Combating Antimicrobial Resistance",slug:"unlocking-the-potential-of-ghost-probiotics-in-combating-antimicrobial-resistance",totalDownloads:20,totalDimensionsCites:0,doi:"10.5772/intechopen.104126",abstract:"Antimicrobial resistance is a global concern that requires immediate attention. Major causes of development of antimicrobial resistance in microbial cells are overuse of antimicrobials along the food chain especially in livestock, in preventing infections as well as misuse of antimicrobials by patients. Probiotics could be a viable alternative to antibiotics in the fight against antimicrobial resistance. Probiotic strains can act as a complement to antimicrobial therapy, improving antimicrobial function and enhancing immunity. However, there are safety concerns regarding the extensive use of live microbial cells especially in immunocompromised individuals; these include microbial translocation, inhibition of other beneficial microorganisms and development of antimicrobial resistance, among other concerns. Inevitably, ghost probiotics have become the favored alternative as they eliminate the safety and shelf-life problems associated with use of probiotics. Ghost probiotics are non-viable microbial cells (intact or broken) or metabolic products from microorganisms, which when administered in adequate amounts have biologic activity in the host and confer health benefits. Ghost probiotics exert biological effects similar to probiotics. However, the major drawback of using ghost probiotics is that the mechanism of action of these is currently unknown, hence more research is required and regulatory instruments are needed to assure the safety of consumers.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Abigarl Ndudzo, Sakhile Ndlovu, Nesisa Nyathi and Angela Sibanda Makuvise"},{id:"82178",title:"Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role of One Health",slug:"managing-antimicrobial-resistance-beyond-the-hospital-antimicrobial-stewardship-the-role-of-one-heal",totalDownloads:16,totalDimensionsCites:0,doi:"10.5772/intechopen.104170",abstract:"Infections caused by micro-organisms affect the health of people and animals, causing morbidity and mortality, with Asia and Africa as the epicenters. Some of the infectious diseases are emerging and re-emerging in nature. Examples include viral hepatitis, Lassa fever, Ebola, yellow fever, tuberculosis, covid-19, measles, and malaria, among others. Antimicrobials have been playing an important role in the treatment of infections by these microbes. However, there has been a development of resistance to these antimicrobials as a result of many drivers. This write-up used secondary data to explore the management of antimicrobial resistance (AMR) beyond the hospital antimicrobial resistance steward using the one health concept. The findings showed AMR to be a transboundary, multifaceted ecosystem problem affecting both the developed and developing countries. It is also one of the top ten global public health threats facing mankind. Globally, AMR will cost over US$100 trillion in output loss by 2050, about 700,000 deaths a year, and 4,150,000 deaths in Africa by 2050. About 2.4 million people could die in high-income countries between 2015 and 2050 without a sustained effort to contain AMR. The drivers of AMR are beyond the hospital and hospital AMR stewardship. Therefore, the need for one health concept to manage it.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Istifanus Anekoson Joshua, Mathew Bobai and Clement Sokfa Woje"},{id:"81918",title:"Machine Learning for Antimicrobial Resistance Research and Drug Development",slug:"machine-learning-for-antimicrobial-resistance-research-and-drug-development",totalDownloads:53,totalDimensionsCites:0,doi:"10.5772/intechopen.104841",abstract:"Machine learning is a subfield of artificial intelligence which combines sophisticated algorithms and data to develop predictive models with minimal human interference. This chapter focuses on research that trains machine learning models to study antimicrobial resistance and to discover antimicrobial drugs. An emphasis is placed on applying machine learning models to detect drug resistance among bacterial and fungal pathogens. The role of machine learning in antibacterial and antifungal drug discovery and design is explored. Finally, the challenges and prospects of applying machine learning to advance basic research on and treatment of antimicrobial resistance are discussed. Overall, machine learning promises to advance antimicrobial resistance research and to facilitate the development of antibacterial and antifungal drugs.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Shamanth A. Shankarnarayan, Joshua D. Guthrie and Daniel A. Charlebois"},{id:"81891",title:"Alternatives to Antibiotics in Semen Extenders Used in Artificial Insemination",slug:"alternatives-to-antibiotics-in-semen-extenders-used-in-artificial-insemination",totalDownloads:29,totalDimensionsCites:0,doi:"10.5772/intechopen.104226",abstract:"Antimicrobial resistance is a serious global threat requiring a widespread response. Both veterinarians and medical doctors should restrict antibiotic usage to therapeutic use only, after determining the sensitivity of the causal organism. However, the addition of antibiotics to semen extenders for animal artificial insemination represents a hidden, non-therapeutic use of antimicrobial substances. Artificial insemination for livestock breeding is a huge global enterprise with hundreds of million sperm doses prepared annually. However, reporting of antimicrobial resistance in semen is increasing. This review discusses the consequences of bacteria in semen samples, as well as the effect of antimicrobial substances in semen extenders on bacteria in the environment and even on personnel. Alternatives to antibiotics have been reported in the scientific literature and are reviewed here. The most promising of these, removal of the majority of bacteria by colloid centrifugation, is considered in detail, especially results from an artificial insemination study in pigs. In conclusion, colloid centrifugation is a practical method of physically removing bacteria from semen, which does not induce antibiotic resistance. Sperm quality in stored semen samples may be improved at the same time.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Jane M. Morrell, Pongpreecha Malaluang, Aleksandar Cojkic and Ingrid Hansson"},{id:"81699",title:"Efflux Pumps among Urinary E. coli and K. pneumoniae Local Isolates in Hilla City, Iraq",slug:"efflux-pumps-among-urinary-e-coli-and-k-pneumoniae-local-isolates-in-hilla-city-iraq",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.104408",abstract:"Urinary tract infections (UTI) are the most common bacterial infections affecting humans. Escherichia coli and Klebsiella pneumoniae were common enterobacteria engaged with community-acquired UTIs. Efflux pumps were vital resistance mechanisms for antibiotics, especially among enterobacteria. Overexpression of an efflux system, which results in a decrease in antibiotic accumulation, is an effective mechanism for drug resistance. The ATP-binding cassette (ABC) transporters, small multidrug resistance (SMR), and multidrug and toxic compound extrusion (MATE) families, the major facilitator superfamily (MFS), and the resistance-nodulation- cell division (RND) family are the five superfamilies of efflux systems linked to drug resistance. This chapter highlights the results of studying the prevalence of efflux pump genes among local isolates of E. coli and K. pneumoniae in Hilla City, Iraq. class RND AcrAB-TolC, AcrAD-TolC, and AcrFE-TolC genes detected by conventional PCR of E. coli and K. pneumoniae respectively. The result revealed approximately all studied efflux transporter were found in both E. coli and K. pneumoniae in different percentages. Biofilm formation were observed in 50(100%) of K. pneumoniae and 49(98%) of E. coli isolates were biofilm former and follow: 30(60%), 20(40%) were weak, 12(24%), 22(44%) were moderate and 7(14%) and 8(16%) were Strong biofilm former for E. coli and K. pneumoniae, respectively.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Hussein Al-Dahmoshi, Sahar A. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"3",title:"Dentistry",doi:"10.5772/intechopen.71199",issn:"2631-6218",scope:"
\r\n\tThis book series will offer a comprehensive overview of recent research trends as well as clinical applications within different specialties of dentistry. Topics will include overviews of the health of the oral cavity, from prevention and care to different treatments for the rehabilitation of problems that may affect the organs and/or tissues present. The different areas of dentistry will be explored, with the aim of disseminating knowledge and providing readers with new tools for the comprehensive treatment of their patients with greater safety and with current techniques. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This series of books will focus on various aspects of the properties and results obtained by the various treatments available, whether preventive or curative.
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He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"1",title:"Oral Health",coverUrl:"https://cdn.intechopen.com/series_topics/covers/1.jpg",isOpenForSubmission:!0,annualVolume:11397,editor:{id:"173955",title:"Prof.",name:"Sandra",middleName:null,surname:"Marinho",slug:"sandra-marinho",fullName:"Sandra Marinho",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGYMQA4/Profile_Picture_2022-06-01T13:22:41.png",biography:"Dr. Sandra A. Marinho is an Associate Professor and Brazilian researcher at the State University of Paraíba (Universidade Estadual da Paraíba- UEPB), Campus VIII, located in Araruna, state of Paraíba since 2011. She holds a degree in Dentistry from the Federal University of Alfenas (UNIFAL), while her specialization and professional improvement in Stomatology took place at Hospital Heliopolis (São Paulo, SP). Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). Dr. Marinho's experience in Dentistry mainly covers the following subjects: oral diagnosis, oral radiology; oral medicine; lesions and oral infections; oral pathology, laser therapy and epidemiological studies.",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"2",title:"Prosthodontics and Implant Dentistry",coverUrl:"https://cdn.intechopen.com/series_topics/covers/2.jpg",isOpenForSubmission:!0,annualVolume:11398,editor:{id:"179568",title:"Associate Prof.",name:"Wen Lin",middleName:null,surname:"Chai",slug:"wen-lin-chai",fullName:"Wen Lin Chai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHGAQA4/Profile_Picture_2022-05-23T14:31:12.png",biography:"Professor Dr. Chai Wen Lin is currently a lecturer at the Department of Restorative Dentistry, Faculty of Dentistry of the University of Malaya. She obtained a Master of Dental Science in 2006 and a Ph.D. in 2011. Her Ph.D. research work on the soft tissue-implant interface at the University of Sheffield has yielded several important publications in the key implant journals. She was awarded an Excellent Exchange Award by the University of Sheffield which gave her the opportunity to work at the famous Faculty of Dentistry of the University of Gothenburg, Sweden, under the tutelage of Prof. Peter Thomsen. In 2016, she was appointed as a visiting scholar at UCLA, USA, with attachment in Hospital Dentistry, and involvement in research work related to zirconia implant. In 2016, her contribution to dentistry was recognized by the Royal College of Surgeon of Edinburgh with her being awarded a Fellowship in Dental Surgery. She has authored numerous papers published both in local and international journals. She was the Editor of the Malaysian Dental Journal for several years. Her main research interests are implant-soft tissue interface, zirconia implant, photofunctionalization, 3D-oral mucosal model and pulpal regeneration.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorTwo:{id:"479686",title:"Dr.",name:"Ghee Seong",middleName:null,surname:"Lim",slug:"ghee-seong-lim",fullName:"Ghee Seong Lim",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003ScjLZQAZ/Profile_Picture_2022-06-08T14:17:06.png",biography:"Assoc. Prof Dr. Lim Ghee Seong graduated with a Bachelor of Dental Surgery from University of Malaya, Kuala Lumpur in 2008. He then pursued his Master in Clinical Dentistry, specializing in Restorative Dentistry at Newcastle University, Newcastle, UK, where he graduated with distinction. He has also been awarded the International Training Fellowship (Restorative Dentistry) from the Royal College of Surgeons. His passion for teaching then led him to join the faculty of dentistry at University Malaya and he has since became a valuable lecturer and clinical specialist in the Department of Restorative Dentistry. He is currently the removable prosthodontic undergraduate year 3 coordinator, head of the undergraduate module on occlusion and a member of the multidisciplinary team for the TMD clinic. He has previous membership in the British Society for Restorative Dentistry, the Malaysian Association of Aesthetic Dentistry and he is currently a lifetime member of the Malaysian Association for Prosthodontics. Currently, he is also the examiner for the Restorative Specialty Membership Examinations, Royal College of Surgeons, England. He has authored and co-authored handful of both local and international journal articles. His main interest is in prosthodontics, dental material, TMD and regenerative dentistry.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:27,paginationItems:[{id:"83092",title:"Novel Composites for Bone Tissue Engineering",doi:"10.5772/intechopen.106255",signatures:"Pugalanthipandian Sankaralingam, Poornimadevi Sakthivel and Vijayakumar Chinnaswamy Thangavel",slug:"novel-composites-for-bone-tissue-engineering",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biomimetics - Bridging the Gap",coverURL:"https://cdn.intechopen.com/books/images_new/11453.jpg",subseries:{id:"8",title:"Bioinspired Technology and Biomechanics"}}},{id:"82800",title:"Repurposing Drugs as Potential Therapeutics for the SARS-Cov-2 Viral Infection: Automatizing a Blind Molecular Docking High-throughput Pipeline",doi:"10.5772/intechopen.105792",signatures:"Aldo Herrera-Rodulfo, Mariana Andrade-Medina and Mauricio Carrillo-Tripp",slug:"repurposing-drugs-as-potential-therapeutics-for-the-sars-cov-2-viral-infection-automatizing-a-blind-",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82582",title:"Protecting Bioelectric Signals from Electromagnetic Interference in a Wireless World",doi:"10.5772/intechopen.105951",signatures:"David Marcarian",slug:"protecting-bioelectric-signals-from-electromagnetic-interference-in-a-wireless-world",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82586",title:"Fundamentals of Molecular Docking and Comparative Analysis of Protein–Small-Molecule Docking Approaches",doi:"10.5772/intechopen.105815",signatures:"Maden Sefika Feyza, Sezer Selin and Acuner Saliha Ece",slug:"fundamentals-of-molecular-docking-and-comparative-analysis-of-protein-small-molecule-docking-approac",totalDownloads:27,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}}]},overviewPagePublishedBooks:{paginationCount:12,paginationItems:[{type:"book",id:"6692",title:"Medical and Biological Image Analysis",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6692.jpg",slug:"medical-and-biological-image-analysis",publishedDate:"July 4th 2018",editedByType:"Edited by",bookSignature:"Robert Koprowski",hash:"e75f234a0fc1988d9816a94e4c724deb",volumeInSeries:1,fullTitle:"Medical and Biological Image Analysis",editors:[{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",slug:"oct-applications-in-ophthalmology",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Michele Lanza",hash:"e3a3430cdfd6999caccac933e4613885",volumeInSeries:2,fullTitle:"OCT - Applications in Ophthalmology",editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}]},{type:"book",id:"6843",title:"Biomechanics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6843.jpg",slug:"biomechanics",publishedDate:"January 30th 2019",editedByType:"Edited by",bookSignature:"Hadi Mohammadi",hash:"85132976010be1d7f3dbd88662b785e5",volumeInSeries:4,fullTitle:"Biomechanics",editors:[{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",institutionURL:null,country:{name:"Canada"}}}]}]},openForSubmissionBooks:{paginationCount:0,paginationItems:[]},onlineFirstChapters:{paginationCount:20,paginationItems:[{id:"82526",title:"Deep Multiagent Reinforcement Learning Methods Addressing the Scalability Challenge",doi:"10.5772/intechopen.105627",signatures:"Theocharis Kravaris and George A. 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The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. 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Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"117248",title:"Dr.",name:"Andrew",middleName:null,surname:"Macnab",slug:"andrew-macnab",fullName:"Andrew Macnab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. 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The scope of this topic will range from molecular, biochemical, cellular, and physiological processes in all animal species. Work pertaining to the whole organism, organ systems, individual organs and tissues, cells, and biomolecules will be included. Medical, animal, cell, and comparative physiology and allied fields such as anatomy, histology, and pathology with physiology links will be covered in this topic. 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